Ultrasound enhancement of cationic lipid-mediated gene transfer to primary tumors following systemic administration
| Autor: | R Earls, I Anscombe, K. Anwer, V Florack, T McCreery, G. Kao, Alain Rolland, E Unger, Sean M. Sullivan, Belinda Proctor, E Wilson |
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| Rok vydání: | 2000 |
| Předmět: |
Genetic enhancement
Gene Expression Biology Transfection Mice Gene expression Genetics Animals Cationic liposome Endothelium Molecular Biology Ultrasonography Mice Inbred C3H Expression vector Genetic transfer Genetic Therapy Neoplasms Experimental Interleukin-12 Molecular biology Platelet Endothelial Cell Adhesion Molecule-1 Microscopy Fluorescence Liposomes Carcinoma Squamous Cell Systemic administration Molecular Medicine Female Sonoporation |
| Zdroj: | Gene Therapy. 7:1833-1839 |
| ISSN: | 1476-5462 0969-7128 |
| DOI: | 10.1038/sj.gt.3301302 |
| Popis: | The impact of a localized application of ultrasound on gene transfer to primary tumors following systemic administration of cationic lipid based transfection complexes was investigated. We have previously shown that systemic administration of DOTMA (N-[(1-(2-3-dioleyloxy) propyl)]-N-N-N-trimethylammonium chloride):cholesterol-based transfection complexes to tumor-bearing mice resulted in expression in the tumor and other tissues, primarily the lungs. Application of ultrasound to the tumor before or after the injection resulted in a significant increase in gene transfer to the tumor with no increase observed in other tissues. The magnitude of increased expression ranged from three- to 270-fold depending upon the DNA dose. The following parameters were optimized for maximal increase: duration of ultrasound application, the time interval between plasmid injection and sonoporation, and plasmid dose. A combination of plasmid quantitation and fluorescence microscopy showed that ultrasound increased tumor uptake of the plasmid and that uptake was limited to the tumor vasculature. Using an IL- 12 expression plasmid, the combination of a single plasmid dose (10 microg) and ultrasound treatment produced significantly higher levels of IL-12 in tumor. This increased expression was sufficient to inhibit tumor growth compared with the control conditions. These data demonstrate the potential application of sonoporation as an effective method for enhancing the expression of systemically administered genes in tumor endothelium for cancer gene therapy. |
| Databáze: | OpenAIRE |
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